Human respiratory syncytial virus (RSV) belongs to the Pneumovirus subfamily of the Paramyxoviridae family with a negative single strand RNA genome and enveloped nucleocapsid (Respiratory Syncytial Virus—Human Paramyxoviridae, Encyclopedia of Virology, Second Edition, G. Allan and G. W. Robert, Eds Oxford, Elsevier, pp. 1479-1487). RSV is the leading cause of pediatric bronchiolitis, pneumonia, and bronchitis worldwide and is also a significant cause of morbidity and mortality in the elderly. Respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory tract disease in infants and children (Feigen et al., eds., 1987, In: Textbook of Pediatric Infectious Diseases, W B Saunders, Philadelphia at pages 1653-1675; New Vaccine Development, Establishing Priorities, Vol. 1, 1985, National Academy Press, Washington D.C. at pages 397-409; and Ruuskanen et al., 1993, Curr. Probl. Pediatr. 23:50-79). The yearly epidemic nature of RSV infection is evident worldwide (Hall, C. B., 1993, Contemp. Pediatr. 10:92-110). Primary RSV infection occurs most often in children from 6 weeks to 2 years of age and uncommonly in the first 4 weeks of life during nosocomial epidemics (Hall et al., 1979, New Engl. J. Med. 300:393-396). Children at increased risk from RSV infection include preterm infants (Hall et al., 1979, New Engl. J. Med. 300:393-396) and children with bronchopulmonary dysplasia (Groothuis et al., 1988, Pediatrics 82:199-203), congenital heart disease (MacDonald et al., New Engl. J. Med. 307:397-400), congenital or acquired immunodeficiency (Ogra et al., 1988, Pediatr. Infect. Dis. J. 7:246-249; and Pohl et al., 1992, J. Infect. Dis. 165:166-169), and cystic fibrosis (Abman et al., 1988, J. Pediatr. 113:826-830). The fatality rate in infants with heart or lung disease who are hospitalized with RSV infection is 3%-4% (Navas et al., 1992, J. Pediatr. 121:348-354).
RSV infects adults as well as infants and children. In healthy adults, RSV causes predominantly upper respiratory tract disease. It has recently become evident that some adults, especially the elderly, have symptomatic RSV infections more frequently than had been previously reported (Evans, A. S., eds., 1989, Viral Infections of Humans. Epidemiology and Control, 3.sup.rd ed., Plenum Medical Book, New York at pages 525-544). Several epidemics also have been reported among nursing home patients and institutionalized young adults (Falsey, A. R., 1991, Infect. Control Hosp. Epidemiol. 12:602-608; and Garvie et al., 1980, Br. Med. J. 281:1253-1254). RSV also may cause serious disease in immunosuppressed persons, particularly bone marrow transplant patients (Hertz et al., 1989, Medicine 68:269-281).
Viral and host factors in human RSV pathogenesis are known (J Virol 82(5): 2040-2055). Two glycoproteins, F and G, on the surface of RSV have been shown to be targets of neutralizing antibodies (Fields et al., 1990, supra; and Murphy et al., 1994, supra). These two proteins are also primarily responsible for viral recognition and entry into target cells; G protein binds to a specific cellular receptor and the F protein promotes fusion of the virus with the cell. The F protein is also expressed on the surface of infected cells and is responsible for subsequent fusion with other cells leading to syncytia formation. Thus, antibodies to the F protein, or other inhibitors of the F protein, may directly neutralize virus or block entry of the virus into the cell or prevent syncytia formation. However, the manufacturing of antibodies is very expensive and the amount of antibody that can be purified and concentrated is limited. To date, no effective vaccine has been developed against RSV due to the lack of suitable animal models and to various immunological obstacles (Crowe Jr, J. E., 2001, Respiratory syncytial virus vaccine development, Vaccine 20, Supplement 1(0): S32-S37). Effective therapeutics and methodologies to eliminate human RSV infection at an early stage are needed. In addition, there is a need to inhibit the fusion process in order to proactively prevent an RSV infection.